Pancreas

Gastroenterology. 2022;163(5):1407–22

Mahajan UM, Oehrle B, Sirtl S, Alnatsha A, Goni E, Regel I, Beyer G, Vornhülz M, Vielhauer J, Chromik A, Bahra M, Klein F, Uhl W, Fahlbusch T, Distler M, Weitz J, Grützmann R, Pilarsky C, Weiss FU, Adam MG, Neoptolemos JP, Kalthoff H, Rad R, Christiansen N, Bethan B, Kamlage B, Lerch MM, Mayerle J

Independent validation and assay standardization of improved metabolic biomarker signature to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis

Background and aims: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy requiring efficient detection when the primary tumor is still resectable. The authors previously developed the MxPancreasScore comprising 9 analytes and serum carbohydrate antigen 19-9 (CA19-9), achieving an accuracy of 90.6%. The necessity for 5 different analytical platforms and multiple analytical runs, however, hindered clinical applicability. They therefore aimed to develop a simpler single-analytical run, single-platform diagnostic signature.
Methods: The authors evaluated 941 patients (PDAC, 356; chronic pancreatitis [CP], 304; non-pancreatic disease, 281) in 3 multicenter independent tests, and identification (ID) and validation cohort 1 (VD1) and 2 (VD2) were evaluated. Targeted quantitative plasma metabolite analysis was performed on a liquid chromatography-tandem mass spectrometry platform. A machine learning-aided algorithm identified an improved (i-Metabolic) and a minimalistic metabolic (m-Metabolic) signature and compared them for performance.
Results: The i-Metabolic signature (12 analytes plus CA19-9) distinguished PDAC from CP with area under the curve of 97.2% (95% confidence interval [CI]: 97.1–97.3%), 93.5% (95% CI: 93.4–93.7%), and 92.2% (95% CI: 92.1–92.3%) in the ID, VD1, and VD2 cohorts, respectively. In the VD2 cohort, the m-Metabolic signature (4 analytes plus CA19-9) discriminated PDAC from CP with a sensitivity of 77.3% and specificity of 89.6%, with an overall accuracy of 82.4%. For the subset of 45 patients with PDAC with resectable stages IA–IIB tumors, the sensitivity, specificity, and accuracy were 73.2%, 89.6%, and 82.7%, respectively; for those with detectable CA19-9 > 2 U/ml, 81.6%, 88.7%, and 84.5%, respectively; and for those with CA19-9 < 37 U/ml, 39.7%, 94.1%, and 76.3%, respectively.

Conclusions: The single-platform, single-run, m-Metabolic signature of just 4 metabolites used in combination with serum CA19-9 levels is an innovative accurate diagnostic tool for pancreatic ductal adenocarcinoma at the time of clinical presentation, warranting further large-scale evaluation.

Prof. Dr. J. Mayerle, Medizinische Klinik II, Klinikum der Universität München – Großhadern, Munich, Germany,
E-Mail: julia.mayerle@med.uni-muenchen.de

DOI: DOI: 10.1053/j.gastro.2022.07.047

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Gut. 2023;72(1):66–72

Boxhoorn L, Verdonk RC, Besselink MG, Boermeester M, Bollen TL, Bouwense SAW, Cappendijk VC, Curvers WL, Dejong CH, van Dijk SM, van Dullemen HM, van Eijck CHJ, van Geenen EJM, Hadithi M, Hazen WL, Honkoop P, van Hooft JE, Jacobs MAJM, Kievits JEC, Kop MPM, Kouw E, Kuiken SD, Ledeboer M, Nieuwenhuijs VB, Perk LE, Poley JW, Quispel R, de Ridder RJJ, van Santvoort HC, Sperna Weiland CJ, Stommel MWJ, Timmerhuis HC, Witteman BJ, Umans DS, Venneman NG, Vleggaar FP, van Wanrooij RLJ, Bruno MJ, Fockens P, Voermans RP; Dutch Pancreatitis Study Group

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